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Molecular and Cellular Biology, February 2008, p. 926-938, Vol. 28, No. 3
0270-7306/08/$08.00+0     doi:10.1128/MCB.01344-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Bypassing the Requirements for Epigenetic Modifications in Gene Transcription by Increasing Enhancer Strength

George Koutroubas, Menie Merika, and Dimitris Thanos^*

Institute of Molecular Biology and Genetics, Biomedical Sciences Research Center A. Fleming, 34 A. Fleming Street, Vari-Athens 16672, Greece

Received 26 July 2007/ Returned for modification 23 August 2007/ Accepted 2 November 2007

Our current concept postulates that histone acetylation is required for the recruitment of bromodomain-containing transcription complexes, such as the chromatin-remodeling machine SWI/SNF and the basal transcription factor TFIID. We generated simple NF-B-dependent enhancers of increasing transcriptional strengths and found that the histone acetylation requirements for activation of transcription depended on the strengths of these enhancers. All enhancers function by recruiting SWI/SNF and TFIID to induce nucleosome sliding, a prerequisite for transcriptional activation. However, histone acetylation, although it occurs, is dispensable for TFIID and SWI/SNF recruitment by the strong enhancers, indicating that strong activators can overcome the chromatin barrier by directly recruiting the necessary transcriptional complexes. Weak enhancers depend on histone acetylation for recruitment, and this requirement is independent of a histone acetylation code. Thus, the need for nucleosome modifications is imposed on genes and translated according to the quality and strengths of the activators.

Published ahead of print on 19 November 2007.

Present address: Institute of Molecular Biology, Genetics and Biotechnology, Foundation for Biomedical Research of the Academy of Athens, 4 Soranou Efesiou Street, Athens 11527, Greece.